Oestrogen induction of progestin receptors in the rat brain and pituitary gland: quantitative and kinetic aspects

Abstract

The processes of oestrogen-receptor binding, translocation and nuclear processing in the pituitary gland, preoptic area (POA), mediobasal hypothalamus (MBH) and amygdala were explored in relation to the induction of cytosol progestin receptors (PR c ). Ovariectomized rats were injected i.v. with a single saturating dose (3·6 μg/kg body wt) of oestradiol-17β (OE 2 ). At various times thereafter cytosol (ER c ) and salt-extractable nuclear (ER n ) oestrogen-receptor concentrations were determined by exchange assay. In all four tissues at 1 h after injection ER c fell and ER n increased, suggesting translocation of ER c into the nucleus. The extent of ER c depletion, however, was not identical in all tissues: substantially less depletion was observed in the amygdala (34%) and POA–MBH (56%) than in the pituitary gland (74%). Depletion of ER c was followed by a phase of replenishment, restoring ER c to preinjection values by 24 h. Concentrations of ER n in all tissues declined between 1 and 24 h, concomitant with the replenishment of ER c . Concentrations of PR c in the pituitary gland and POA–MBH increased during the first 12 h after injection of OE 2 to a plateau value between 12 and 24 h, then declined to control values by 72 h. No induction of PR c was seen in the amygdala. A second injection of OE 2 2 h after the first injection refilled the nuclear binding sites, restoring ER n to levels indistinguishable from those seen 1 h after a single OE 2 treatment. The extent of ER c depletion after two injections with OE 2 was, however, proportionately less than that seen after a single treatment with OE 2 . The second OE 2 injection raised PR c concentrations above those seen after a single injection in the POA–MBH but not in the pituitary gland. When the two OE 2 injections were more widely spaced (14 h apart) the PR c response in both the pituitary gland and POA–MBH was greater than after a single OE 2 injection, and was comparable to that seen in animals given a very large dose (360 μg/kg body wt) of OE 2 . These results confirm the existence of differences between the pituitary gland, POA–MBH and amygdala in the ER c and PR c responses to oestrogen treatment. In addition, they suggest that the PR c response of the pituitary gland and POA–MBH to OE 2 is influenced by previous exposure to OE 2 .